Viral myocarditis: 1917–2020: From the Influenza A to the COVID-19 pandemics

Myocarditis is common during viral infection with cases described as early as the influenza pandemic of 1917, and the current COVID-19 pandemic is no exception. The hallmark is elevated troponin, which occurs in 36% of COVID patients, with electrocardiogram, echocardiogram, and cardiac magnetic resonance being valuable tools to assist in diagnosis. Cardiac inflammation may occur secondary to direct cardiac invasion with the virus, or to intense cytokine storm, often encountered during the course of the disease. Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and judicious use of beta-blockers are beneficial in management of myocarditis. Corticosteroids may be avoided during the very early phase of viral replication, but can be of clear benefit in hospitalized, critically ill patients. Statins are beneficial to shorten the course of the disease and may decrease mortality.     

Use of nifedipine as an adjunct to current antihypertensive therapy

Ten hypertensive patients with poor responses to standard antihypertensive therapy were treated with the calcium channel antagonist nifedipine in an attempt to obtain better BP control. The drug was highly effective in significantly lowering BP immediately (average decrease, 58/29 mm Hg) and after three to eight weeks of maintenance therapy (average decrease, 49/27 mm Hg), with no significant change in heart rate observed at either time. No adverse interactions between nifedipine and other concurrent medications, including digoxin and beta-adrenergic blockers, were noted. Drug-related side effects of tachycardia or flushing necessitated the withdrawal of nifedipine therapy in two patients. We conclude that nifedipine may be safely employed in an outpatient setting as a useful adjunct to current antihypertensive drug regimens.     

A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension

PURPOSE: Antihypertensive medications have different effects on left ventricular mass. We conducted a meta-analysis of double-blind trials that measured the effects of antihypertensive therapy on left ventricular mass. METHODS: Medical databases and review articles were screened for double-blind, randomized controlled trials (through September 2002) that reported the effects of diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin II receptor antagonists on echocardiographic left ventricular mass in essential hypertension. Treatment arms of the same drug class, weighted for the number of patients, were combined. Analysis of covariance was performed to detect differences among drug classes in effects on left ventricular structure. RESULTS: Eighty trials with 146 active treatment arms (n = 3767 patients) and 17 placebo arms (n = 346 patients) were identified. Adjusted for treatment duration and change in diastolic blood pressure, there was a significant difference (P = 0.004) among medication classes: left ventricular mass index decreased by 13% with angiotensin II receptor antagonists (95% confidence interval [CI]: 8% to 18%), by 11% with calcium antagonists (95% CI: 9% to 13%), by 10% with ACE inhibitors (95% CI: 8% to 12%), by 8% with diuretics (95% CI: 5% to 10%), and by 6% with beta-blockers (95% CI: 3% to 8%). In pairwise comparisons, angiotensin II receptor antagonists, calcium antagonists, and ACE inhibitors were more effective at reducing left ventricular mass than were beta-blockers (all P <0.05 with Bonferroni correction). CONCLUSIONS: Antihypertensive drug classes have different effects on left ventricular mass reduction. Whether a greater reduction of left ventricular mass results in better clinical outcomes remains to be determined.     

Acute and long-term treatment of hypertension with nifedipine in the elderly

The acute hypotensive effect of nifedipine was evaluated, and the possibility of its long-term use in hypertensives over 60 years of age was studied. Sublingual nifedipine in a dose of 20 mg was given to 28 patients, mean age 73.1 yrs, and blood pressure, heart rate, and plasma drug concentration were monitored at 15 min, and every 30 min thereafter for 3 hrs. Systolic and diastolic blood pressure decreased at 15 min by 22.1 and 7.0 mmHg, respectively, reaching a maximal decrease two hours after drug administration. The decrease in blood pressure level did not correlate with nifedipine plasma concentration, but only with the initial systolic blood pressure. Long-term treatment with nifedipine was initiated in 60 patients, with 45 patients completing the study. Mean age was 66.2 years. An initial dose of 30 mg daily had to be increased to 60-80 mg in one-third of the patients. Monotherapy was not satisfactory in some patients. Blood pressure gradually decreased from 173/99 to 148/85 mmHg at three months, and to 141/84 mmHg at six months. Drug tolerance was fairly good. Nifedipine was withdrawn due to a considerable increase in heart rate in three patients and skin allergy in one. The most frequent adverse symptoms were: rash, headache, and leg oedema. Laboratory tests revealed no changes in urea and creatinine, and an increase in fasting glycaemia. Lipid parameters did not change significantly. These data proved that a single dose of 20 mg of nifedipine produced therapeutic plasma concentration of the drug and good hypotensive effect, positively correlating with initial systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temporal improvement in heart failure survival related to the use of a nurse-directed clinic and recommended pharmacological treatment

BACKGROUND: The use of recommended drugs for chronic heart failure (CHF) has been discouragingly low in clinical practice. The aim of this study was to prospectively evaluate to which extent a nurse-directed heart failure clinic could accomplish drug titration with modern heart failure treatments, with focus on beta-blockers. METHODS: Outcome of drug titration was evaluated for 418 patients referred to the nurse-run clinic from 1995 through 2001, using a prospective, open, non-randomised quality control protocol. RESULTS: Throughout the period, most of the patients were discharged on an ACE inhibitor (during 2001, 86%). The use of beta-blockers increased during the observation (from 43% to 88%). Patients started on an ACE-inhibitor treatment continued in 89% and in 95% when started on a beta-blocker. There was a significant decrease in mortality, relative risk per year 0.84 (95% CI, 0.75 to 0.94), P=0.002. Three-year mortality was reduced from 27% to 10%. In a multivariable analysis, survival was significantly associated with ejection fraction, renal function, the use of beta-blockers and ACE inhibitors, and negatively with digitalis treatment. CONCLUSIONS: The nurse-directed titration succeeded in introducing more patients on beta-blockers than on ACE-inhibitors. Mortality was reduced during the study period, associated with more use of documented therapy, beta-blockers in particular. These findings suggest that the observed signs of improvement in CHF prognosis are likely caused by more efficient medical treatment.     

The long-term effect of nifedipine (control release tablets) in patients with chronic obstructive pulmonary disease and cor pulmonale]

OBJECTIVE: To observe the long-term effect of nifedipine (control release tablets) in patients with chronic obstructive pulmonary disease and cor pulmonale. METHODS: A randomized, double blind, placebo-controlled design was made, two hundred and two patients (FEV1/FVC was 47.35% +/- 8.10%) were divided into two groups: nifedipine group (20 mg Bid) 102 cases, placebo group (one tablet Bid) 100 cases. RESULTS: The equilibrium test between both groups was comparable. Two-year follow-up rates of both groups were 94% and 89%, respectively. The comparision of the nifedipine to placebo group was as follows: in nifedipine group, the improvement of dyspnea, fatigue and exercise capacity showed significantly better results (P < 0.05); FEV1 and PaCO2 deterioration was unremarkable (P > 0.05); the pulmonary impedance plethysmogram B-Y1 that reflects pulmonary vascular compliance appeared significant improvement (P < 0.05) and the mortality of the disease that was the most important observation endpoint was declined (P = 0.051), but some electrocardiographic index reflected right ventricular load became worse (P < 0.05). CONCLUSIONS: Long-term taking controlled release-nifedipine is a safe, effective measure which might improve life quality and decrease mortality in patients with chronic obstructive pulmonary disease and chronic cor pulmonale, however the drug can not slow down or reverse the progress of this illness.     

Changing patterns of initial drug therapy for the treatment of hypertension in a Medicaid population, 2001-2005

Thiazide diuretics have been recommended as one preferred choice for the initial treatment of hypertension. This study was undertaken to determine whether Maine physicians initiating monotherapy for newly diagnosed hypertensive patients from 2001-2005 used this guideline. The Maine Medicaid database was searched for the drug classes used to initiate monotherapy for patients followed for at least 6 months. A total of 5373 patients were included. In 2001, the use of beta-blockers was 23.5%, diuretics 17.5%, angiotensin-converting enzyme inhibitors 37.5%, calcium channel blockers 9.5%, angiotensin receptor blockers 3.8%, and others 8.2%. By 2005, the use of beta-blockers was 27.8%, diuretics 25.5%, angiotensin-converting enzyme inhibitors 30.9%, calcium channel blockers 6.4%, angiotensin receptor blockers 1.6%, and others 7.7%. There was an increase in the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in diabetics but no other condition affected drug choice. Although there was an increase in the use of diuretics as initial therapy in 2003 and 2004, this decreased in 2005. The increase in initial diuretic use was not reflected in patterns of ongoing antihypertensive use from 1997 to 2005. There appears to have been limited impact from the guidelines on initial drug choice and even less so on ongoing drug therapy.     

Similarities and differences in the antihypertensive effect of two calcium antagonist drugs, verapamil and nifedipine

The short- and long-term effects of two calcium channel blocking drugs, verapamil and nifedipine, on blood pressure, heart rate, plasma catecholamines, plasma renin activity, plasma volume and cardiac performance (echocardiography) were studied in essential hypertensive patients and in normal subjects. Verapamil, 160 mg orally, reduced blood pressure within 60 minutes in 22 hypertensive patients, but not in 12 normotensive subjects. Nifedipine, 10 mg sublingually, reduced blood pressure within 15 minutes in 19 hypertensive patients, but not in 7 normotensive subjects. Plasma noradrenaline was significantly increased both in normal subjects and in hypertensive patients only after nifedipine was administered. Verapamil (80 mg three times a day) first, and nifedipine (10 mg three times a day) thereafter, or vice versa, were given to 12 hospitalized hypertensive patients on a fixed sodium and potassium intake; the drugs produced similar blood pressure reductions, but heart rate and plasma catecholamines were increased only after nifedipine (p less than 0.05). Neither drug affected plasma volume, aldosterone or plasma renin activity. Long-term ambulatory treatment with verapamil (80 or 160 mg three times a day for 2 to 4 months) or nifedipine (10 mg three times a day for 2 months) produced changes in all variables that were similar to those observed in the hospital (controlled) study. Shortening fraction was significantly increased after nifedipine (p less than 0.05) but no change was observed after verapamil. In conclusion, blood pressure is effectively reduced by both verapamil and nifedipine; an appreciable adrenergic stimulation may be caused by nifedipine, but usually not by verapamil, and fluid retention, renin release or myocardial depression is not observed during verapamil or nifedipine treatment.     

Trends in heart failure outcomes and pharmacotherapy: 1992 to 2000

PURPOSE: To review trends in drug therapy and concomitant outcomes of elderly heart failure patients in Ontario, Canada. METHODS: Utilization of drug therapies, mortality, and rehospitalization rates from April 1992 to March 2000 were determined in 77,421 elderly (aged >/=65 years), community-based heart failure patients using linked administrative databases. Treatment effects were identified from published meta-analyses and randomized trials. The effect of drug trends on mortality and morbidity were assessed based on their absolute treatment effects. RESULTS: From 1992 to 2000, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use increased from 58% to 62% (P = 0.001) while beta-blocker use increased from 6% to 22% (P <0.001). There was a decrease in the use of treatments for which no survival advantage had been demonstrated in randomized trials, such as digitalis (49% to 35%, P <0.001), Vaughan-Williams class I antiarrhythmic agents (3.5% to 1.4%, P <0.001), and first-generation calcium antagonists (21.3% to 9.6%, P <0.001). The trends in drug therapy were associated with a 2.8% reduction in age-, sex-, and comorbidity-adjusted 1-year mortality and a 4.1% reduction in 1-year hospitalization rates. The observed trends in therapy over time explained 37% of the decrease in mortality and 30% of the decrease in rehospitalization rates. The treatment effect from beta-blockers was most pronounced, explaining 30% of the decrease in mortality and 10% of the decrease in rehospitalization rates. CONCLUSION: During 1992 to 2000, mortality and morbidity improved among elderly patients with heart failure, with increased utilization of beta-blockers contributing most to the beneficial trends in outcomes.     

Antihypertensive drug therapy in Saskatchewan: patterns of use and determinants in hypertension

BACKGROUND: The benefits of continuous treatment of hypertension have been extensively documented in randomized controlled trials. However, clinical trials may not reflect actual drug use in the population. OBJECTIVE: To examine the distribution and determinants of patterns of use of antihypertensive agents in the first 5 years of hypertension treatment in Saskatchewan. METHODS: Patterns of use and modifications to therapy were derived from a careful examination of medication use in a cohort of 19 501 subjects aged 40 to 79 years, without recognized cardiac disease and initiating therapy with an angiotensin-converting enzyme inhibitor, a calcium antagonist, or a beta-blocker in Saskatchewan between 1990 and 1993. RESULTS: Angiotensin-converting enzyme inhibitors (37.4%), followed by calcium antagonists (27.5%) and beta-blockers (26.4%), were the most commonly prescribed agents to initiate treatment in our study population. Patients with diabetes were less likely to be dispensed a beta-blocker, as were younger and female patients. Previous visits to a cardiologist decreased the likelihood of receiving combination therapy or angiotensin-converting enzyme inhibitors but increased that of using calcium antagonists. Apart from dose adjustment, 89% of study subjects underwent at least 1 modification to their initial regimen, at a median time of 134 days. After 1 year, only 33.8% of patients were still using their initial drug. An early decrease in the proportion of patients continuing to receive initial therapy was noted, especially among beta-blocker users. CONCLUSIONS: Erratic drug-taking behaviors were observed in this Saskatchewan population. In addition, initial drug use does not seem to be in accordance with the stepped-care approach to hypertension therapy recommended in the Canadian guidelines.     

Antihypertensive therapy at the onset of an acute myocardial infarction predicts in-hospital mortality

Several studies, which have compared the efficacy of conventional antihypertensive drugs (thiazide diuretics and beta-blockers) with the newer agents [calcium blockers and angiotensin-converting enzyme (ACE) inhibitors], have shown that they are almost equally efficacious with regard to effects on blood pressure, and in preventing cardiovascular morbidity and mortality. The potential value of these drugs when hypertensive patients suffer an acute myocardial infarction (AMI) has, however, not been fully elucidated. The objective of the present observational study was to investigate whether prior use of different antihypertensive drugs could modify or influence in-hospital death in hypertensives suffering an AMI. A total of 299 hypertensive patients with the diagnosis of AMI were included. The demographic data were obtained from medical records. Variables were entered into a logistic regression model. The main predictors of death were age (adjusted odds ratio (ORa) 1.07, p = 0.002 (per each year), and the use of diuretics (ORa 2.54, p = 0.018) and calcium blockers (ORa 2.54, p = 0.010). On the other hand, the use of ACE inhibitors was associated with a marked reduction of in-hospital death (ORa 0.44, p = 0.045). The present study indicates that while the use of ACE inhibitors was associated with a reduced risk of in-hospital death in hypertensive patients suffering an AMI, the use of diuretics and calcium blockers was associated with increased risks.     

Outcome With Calcium Channel Antagonists After Myocardial Infarction: A Community-Based Study

Objectives. We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study.Background. Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established.Methods. Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates.Results. From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared with patients taking neither calcium antagonists nor beta-blockers.Conclusions. These results are consistent with randomized trial data showing benefit from beta-blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta-blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists.     

Treatment of angina pectoris with nifedipine and atenolol: efficacy and effect on cardiac function

The antianginal effects of nifedipine 20 mg three times a day and atenolol 100 mg once a day singly and in combination were investigated in 16 patients with angina pectoris. The amount of work that could be done before angina and ST depression appeared was significantly increased by atenolol and the combination but not by nifedipine. At peak exercise the number of leads on a 16 point precordial electrocardiogram map that demonstrated greater than or equal to 1 mm ST segment depression was significantly reduced from a mean (SD) of 5.0 (0.4) on placebo to 3.7 (0.6), 2.8 (0.4), and 2.3 (0.7) on nifedipine, atenolol, and the combination respectively. Mean resting left ventricular ejection fraction, assessed by gated radionuclide ventriculography, did not change during any active treatment phase but increased significantly during exercise only on nifedipine and the combination. The nifedipine/atenolol combination was the most effective treatment, and the data suggest that nifedipine may be used to best advantage in combination with a beta blocker.     

Treatment of angina pectoris with nifedipine and atenolol: efficacy and effect on cardiac function.

The antianginal effects of nifedipine 20 mg three times a day and atenolol 100 mg once a day singly and in combination were investigated in 16 patients with angina pectoris. The amount of work that could be done before angina and ST depression appeared was significantly increased by atenolol and the combination but not by nifedipine. At peak exercise the number of leads on a 16 point precordial electrocardiogram map that demonstrated greater than or equal to 1 mm ST segment depression was significantly reduced from a mean (SD) of 5.0 (0.4) on placebo to 3.7 (0.6), 2.8 (0.4), and 2.3 (0.7) on nifedipine, atenolol, and the combination respectively. Mean resting left ventricular ejection fraction, assessed by gated radionuclide ventriculography, did not change during any active treatment phase but increased significantly during exercise only on nifedipine and the combination. The nifedipine/atenolol combination was the most effective treatment, and the data suggest that nifedipine may be used to best advantage in combination with a beta blocker.     

Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study

BACKGROUND: Cardiovascular diseases are associated with disturbances in calcium metabolism, including increased urinary calcium, vitamin D insufficiency, and decreased bone mineral density. Antihypertensive drugs may increase the risk of falling. However, risk of fracture in patients treated with non-diuretic cardiovascular drugs is largely unknown. AIM: We investigated associations between fracture risk and treatment with commonly used cardiovascular drugs: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium-channel blockers. DESIGN: A population-based pharmaco-epidemiological case-control study with fracture in year 2000 as outcome and drug use during the previous 5 years as exposure. We used nationwide computerized registers to assess individual use of drugs and related these data to individual fracture records and information on socio-economic and health-related confounders. RESULTS: We included 124,655 cases that sustained a fracture and 373,962 age and gender-matched controls. After adjustment for potential confounders, risk of any fracture was reduced by 9% [odds ratio (OR) 0.91; 95% confidence interval (CI), 0.88-0.93] in users of beta-blockers, by 6% (OR, 0.94; 95%CI, 0.91-0.96) in users of calcium-channel blockers, and by 7% (OR, 0.93; 95%CI, 0.90-0.96) in users of ACE inhibitors. Moreover, risk of hip fractures was reduced significantly by 7-14% in users of the three groups of drugs. No major differences were found between men and women or in subjects younger or older than 70 years of age. Sub-analyses indicated differences between groups of calcium-channel blockers, as use of non-dihydropyridine drugs was associated with a larger risk reduction than use of dihydropyridine drugs. CONCLUSION: Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a small but significantly reduced risk of fracture.